2-Bromo-5-fluoropyrazine synthesis

Yield: 75%

Reaction Conditions:

with trifluoromethylsulfonic anhydride in pyridine at 0 - 20;

Steps:

27.C Part C
4.2 g (24 mmol) of the product from Part B was dissolved in pyridine (25 mL) and cooled to 0° C. in an ice bath. Triflic anhydride (Aldrich, 8.12 g, 28.8 mmol) was added in several portions over approximately 5 min. The mixture was allowed to mix, stoppered with a syringe needle vent in an ice bath for approximately 30 min, and then stoppered overnight at ambient temperature. The reaction mixture with diethyl ether (300 mL) and aqueous 1N HCl (500 mL). Separated layers and back-extracted the aqueous layer with diethyl ether (200 mL). The combined organic extracts were washed with saturated aqueous NaHCO3 (2?100 mL ) and saturated aqueous NaCll (200 mL). The organic layers were dried over MgSO4, filtered, and concentrated in vacuo to an oil that was purified by chromatography (silica, ethyl acetate/hexanes) to produce 5.55 g (75%) of the desired product. 1H NMR confirmed the structure of the product.

References:

Barta, Thomas E.;Becker, Daniel P.;Bedell, Louis J.;Boehm, Terri L.;Brown, David L.;Carroll, Jeffery N.;Chen, Yiyuan;Fobian, Yvette M.;Freskos, John N.;Gasiecki, Alan F.;Grapperhaus, Margaret L.;Heintz, Robert M.;Hockerman, Susan L.;Kassab, Darren J.;Khanna, Ish K.;Kolodziej, Stephen A.;Massa, Mark A.;McDonald, Joseph J.;Mischke, Brent V.;Mischke, Deborah A.;Mullins, Patrick B.;Nagy, Mark A.;Norton, Monica B.;Rico, Joseph G.;Schmidt, Michelle A.;Stehle, Nathan W.;Talley, John J.;Vernier, William F.;Villamil, Clara I.;Wang, Lijuan J.;Wynn, Thomas A. US2005/9838, 2005, A1 Location in patent:Page 150